dpx-survivac and pembrolizumab with and without intermittent low-dose cyclophosphamide, in subjects with relapsed/refractory diffuse large b-cell lymphoma

Conditions: Relapsed Diffuse Large B-cell Lymphoma; Refractory Diffuse Large B-cell Lymphoma

Summary: this is a phase 2b, randomized, open label study to assess the safety and efficacy of dpx-survivac and pembrolizumab, with and without low-dose cyclophosphamide (cpa) in subjects with relapsed or refractory dlbcl.

this is a phase 2b, randomized, open label study to assess the safety and efficacy of dpx-survivac and pembrolizumab, with and without low-dose cyclophosphamide (cpa) in subjects with relapsed or refractory dlbcl. the study will enroll up to 102 subjects. eligible subjects will be randomized (1:1) to receive: * arm 1: dpx-survivac, pembrolizumab and intermittent, low-dose cpa; or, * arm 2: dpx-survivac and pembrolizumab all subjects will receive two 0.5 ml doses of dpx-survivac 3 weeks apart on day 7 (d7) and d28 followed by up to twelve 0.1 ml doses of dpx-survivac, 8 weeks apart (q8w). all subjects will receive pembrolizumab intravenously (iv) at a flat dose of 200 mg starting at d7 and on day 1 of each 3-week cycle thereafter (i.e., d28, d49, d70 etc.) (q3w). for subjects randomized to arm 1, intermittent oral cpa at a dose of 50 mg twice a day (bid) is administered from d0 to d6 (7 days) followed by 7 days off. this 14-day cycle of "7 days on and 7 days off" will be repeated until the end of study treatment.

Eligibility criteria:
key inclusion criteria: * adults ≥ 18 years of age who are willing and able to provide written informed consent * have an ecog performance status of ≤ 1. subjects with an ecog performance status of 2 may be enrolled with medical monitor approval. * pathologically confirmed diagnosis of dlbcl, as defined by the 2016 world health organization classification including dlbcl nos high-grade b-cell lymphoma with myc and bcl2 and/or bcl6 rearrangements, epstein-barr virus (ebv) positive dlbcl, and t cell rich b cell lymphoma (tcrbcl). subjects with dlbcl transformed from indolent lymphoma (except for richter's transformation) are eligible. * subjects must have progressive disease following at least two (2) lines of prior systemic therapy for dlbcl; prior treatment must have included an anthracycline and rituximab (or another cd20-targeted agent). * subjects must have failed or be ineligible for asct or car-t * have at least one bi-dimensionally measurable lesion per lugano (2014) * willing to provide pre-treatment and on-treatment tumor biopsy tissue. * meet protocol-specified laboratory requirements * life expectancy \> 3 months. key exclusion criteria: * primary cns lymphoma or active secondary cns involvement and/or lymphomatous meningitis * chemotherapy, immunotherapy, major surgery, or investigational agent treatment within 28 days of d0 or 5 half-lives, whichever is shorter * radiotherapy within 14 days of day 0 * autologous stem cell transplant (asct) within ˂100 days prior to d0 * chimeric antigen receptor t cell (car-t) therapy within ˂28 days prior to d0 * diagnosis of immunodeficiency disorder or history of active autoimmune disease that has required systemic treatment in the past 2 years * uncontrolled significant active infections (controlled hepatitis b, hepatitis c, or hiv may be eligible) * prior history of malignancy other than eligible lymphoma sub-types, unless the subject has been free of the disease for ≥ 2 years prior to the start of study treatment

Keywords: immunotherapy t cell activation dlbcl anti-pd-1 car-t ineligible asct ineligible